New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

Panic disorder patients are vulnerable to recurrent panic attacks. Two neurochemical hypotheses have been proposed to explain this susceptibility. The first assumes that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organize defensive reactions to cope with proximal threats and of sympathomotor control areas of the rostral ventrolateral medulla that generate most of the neurovegetative symptoms of the panic attack. The second suggests that endogenous opioids buffer normal subjects from the behavioral and physiological manifestations of the panic attack, and their deficit brings about heightened suffocation sensitivity and separation anxiety in panic patients, making them more vulnerable to panic attacks. Experimental results obtained in rats performing one-way escape in the elevated T-maze, an animal model of panic, indicate that the inhibitory action of serotonin on defense is connected with activation of endogenous opioids in the periaqueductal gray. This allows reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the fulcrum of serotonin-opioid interaction.

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.

Journal du Camp de Gray commandé par M. Le duc de Randan

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 26. au 27. aoust

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 2. au 3. 7.bre 1754

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 3. au 4. 7.bre 1754

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Du 4. au 5.

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 5. au 6. 7.bre

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 6. au 7. 7.bre 1754

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 7. au 8. 7.bre 1754

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 8. au 9. 7.bre 1754

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 9. au 10. 7.bre 1754

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 10. au 11. 7.bre 1754

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

[Journal du Camp de Gray commandé par M. Le duc de Randan]. Ordre du 11. au 12. 7.bre

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')